Triclosan targets lipid synthesis

McMurry, Laura M.; Oethinger, Margret; Levy, Stuart B.

doi:10.1038/28970

Cited by 935 publications

(753 citation statements)

References 8 publications

(1 reference statement)

Supporting

Mentioning

720

Contrasting

Unclassified

Order By: Relevance

“…[1,2-14 C]acetate (50 Ci/ml [60 mCi/mmol] sodium acetate; NEN) was added. After 2 h, the parasites were isolated, washed thoroughly with phosphate-buffered saline, lysed, sonicated, spotted onto a Whatman 3MM paper disk, and counted in scintillation fluid for estimation of the level of incorporation of [ 14 C]acetate into fatty acids (18). The pretreated cultures were also analyzed for inhibition of growth by microscopy and by monitoring the incorporation of [ 35 S]methionine (10 mCi/ml, 1,175 Ci/mmol; NEN) into the proteins.…”

Section: Methodsmentioning

confidence: 99%

Inhibitors of Nonhousekeeping Functions of the Apicoplast Defy Delayed Death in Plasmodium falciparum

Ramya

Mishra

Karmodiya

et al. 2007

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Targeting of apicoplast replication and protein synthesis in the apicomplexan Toxoplasma gondii has conventionally been associated with the typical "delayed death" phenotype, characterized by the death of parasites only in the generation following drug intervention. We demonstrate that antibiotics like clindamycin, chloramphenicol, and tetracycline, inhibitors of prokaryotic protein synthesis, invoke the delayed death phenotype in Plasmodium falciparum, too, as evident from a specific reduction of apicoplast genome copy number. Interestingly, however, molecules like triclosan, cerulenin, fops, and NAS-91, inhibitors of the recently discovered fatty acid synthesis pathway, and succinyl acetone, an inhibitor of heme biosynthesis that operates in the apicoplast of the parasite, display rapid and striking parasiticidal effects. Our results draw a clear distinction between apicoplast functions per se and the apicoplast as the site of metabolic pathways, which are required for parasite survival, and thus subserve the development of novel antimalarial therapy.

show abstract

Section: Methodsmentioning

confidence: 99%

Inhibitors of Nonhousekeeping Functions of the Apicoplast Defy Delayed Death in Plasmodium falciparum

Ramya

Mishra

Karmodiya

et al. 2007

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…36,37,75,76 Of the seven variants, only four had measurable activity, F93V, R96M, R96G, and F203L (Table 1). The F93V and F203L variants had significant reductions in activity (126−190-fold reduction in k cat ).…”

Section: Journal Of Medicinal Chemistrymentioning

confidence: 99%

3-Substituted Indole Inhibitors Against Francisella tularensis FabI Identified by Structure-Based Virtual Screening

Compton

AbdulHameed

et al. 2013

J. Med. Chem.

View full text Add to dashboard Cite

In this study, we describe novel inhibitors against Francisella tularensis SchuS4 FabI identified from structure-based in silico screening with integrated molecular dynamics simulations to account for induced fit of a flexible loop crucial for inhibitor binding. Two 3-substituted indoles, 54 and 57, preferentially bound the NAD + form of the enzyme and inhibited growth of F. tularensis SchuS4 at concentrations near that of their measured K i . While 57 was species-specific, 54 showed a broader spectrum of growth inhibition against F. tularensis, Bacillus anthracis, and Staphylococcus aureus. Binding interaction analysis in conjunction with site-directed mutagenesis revealed key residues and elements that contribute to inhibitor binding and species specificity. Mutation of Arg-96, a poorly conserved residue opposite the loop, was unexpectedly found to enhance inhibitor binding in the R96G and R96M variants. This residue may affect the stability and closure of the flexible loop to enhance inhibitor (or substrate) binding.

show abstract

“…Some inhibitors of other bacterial FAS are known. Triclosan and isoniazid, which are currently used antibacterial agents, have been demonstrated to act by inhibiting FabI [5,6]. Cephalochromin and unsaturated fatty acids acting as FabI inhibitors [7,8], atromentin acting as a FabK inhibitor [9], cerulenin and thiolactomycin acting as FabH/B inhibitors [3], and platensimycin and phomallenic acid acting as FabF inhibitors [10,11] were isolated from microorganisms.…”

mentioning

confidence: 99%

Macrolactin S, a New Antibacterial Agent with Fab G-inhibitory Activity from Bacillus sp. AT28

2008

View full text Add to dashboard Cite

In the course of screening for FabG inhibitors from microbial sources, a new 24-membered ring lactone named macrolactin S, along with the known compound macrolactin B, has been isolated from the mycelium of liquid fermentation cultures of Bacillus sp. AT28. The structure of macrolactin S was determined on the basis of MS and NMR data. Macrolactin S showed a dosedependent inhibition of Staphylococcus aureus FabG, not inhibiting S. aureus FabI. Also macrolactin S inhibited the growth of S. aureus, Bacillus subtilis, and Escherichia coli.

show abstract

Triclosan targets lipid synthesis

Cited by 935 publications

References 8 publications

Inhibitors of Nonhousekeeping Functions of the Apicoplast Defy Delayed Death in Plasmodium falciparum

Inhibitors of Nonhousekeeping Functions of the Apicoplast Defy Delayed Death in Plasmodium falciparum

3-Substituted Indole Inhibitors Against Francisella tularensis FabI Identified by Structure-Based Virtual Screening

Macrolactin S, a New Antibacterial Agent with Fab G-inhibitory Activity from Bacillus sp. AT28

Contact Info

Product

Resources

About